Resurgence of H5N6 avian influenza virus in 2021 poses new threat to public health
Authors: Jiahao Zhang, Hejia Ye, Yi Liu, Ming Liao, Wenbao Qi
Journal: The Lancet Microbe (2022)

First identified as belonging to the H5N1 subtype in Guangdong province, China, in 1996, the Gs/GD lineage H5 avian influenza viruses have continuously evolved and spread since.1Wille M Barr IG Resurgence of avian influenza virus.Science. 2022; 376: 459-460Crossref PubMed Scopus (7) Google Scholar, 2Dai M Yan N Huang Y Zhao L Liao M Survivability of highly pathogenic avian influenza virus on raw chicken meat in different environmental conditions.Lancet Microbe. 2022; 3: e92Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar H5 subtype viruses evolved into multiple distinct subclades, among which 2.3.4.4 has become dominant in China,3Yamaji R Saad MD Davis CT et al.Pandemic potential of highly pathogenic avian influenza clade 2.3.4.4 A(H5) viruses.Rev Med Virol. 2020; 30e2099Crossref PubMed Scopus (34) Google Scholar and H5N6 viruses of this subclade led to an apparent increase in human infections in 2021 and 2022. During this period, 33 cases (of a total of 76 recorded cases infected with subclade 2.3.4.4 H5N6 viruses) have been documented, resulting in 11 deaths and posing an alarming threat to public health.1Wille M Barr IG Resurgence of avian influenza virus.Science. 2022; 376: 459-460Crossref PubMed Scopus (7) Google Scholar Almost all confirmed cases were in individuals who had reported exposure to poultry. To address concerns regarding the sharp increase in the number of human infections, we explored the evolutionary dynamics and conducted a risk assessment of H5N6 viruses from birds in live poultry markets during 2021.In 2021, 5883 cloacal and tracheal swab samples from chickens, ducks, and geese were obtained from live poultry markets in China and analysed for influenza viruses (appendix pp 9–13). We determined the full-length genomes of 19 H5N6 viruses from chickens, ducks, and geese and found that the genomes of these viruses were more complex than those of H5N6 viruses circulating in China previously (appendix pp 2–3). Of particular concern is that the genomes of all H5N6 viruses were continuously reassorted with those of 2.3.4.4b H5N8 viruses of wild bird-origin, and were genetically closely related to the H5N6 virus that infected humans in 2021 (appendix pp 2–3, 14–28). We found that these 2.3.4.4b H5N6 viruses were novel reassortants. The HA and M genes of all isolates were derived from 2.3.4.4b H5N8 viruses of wild-bird origin, whereas other internal genes of all isolates exhibited several separate clusters. On the basis of phylogenetic trees, we identified five distinct genotypes of H5N6 viruses (G1–G5; appendix pp 3, 28), and found that both the G1 and G3 genotype H5N6 viruses were 100% lethal to mice (appendix pp 3–4, 28–29). The high genetic diversity and the virulence in mammals of H5N6 viruses in 2021 pose an increasing threat to public health. During the 2020–21 influenza season, novel H5N8 viruses repeatedly entered Europe, Russia, South Korea, and China, causing numerous outbreaks in wild birds and poultry.4Zhang J Li X Wang X et al.Genomic evolution, transmission dynamics, and pathogenicity of avian influenza A (H5N8) viruses emerging in China, 2020.Virus Evol. 2021; 7veab046Crossref Scopus (11) Google Scholar Notably, these H5N8 viruses infected humans in Russia,5Pyankova OG Susloparov IM Moiseeva AA et al.Isolation of clade 2.3.4.4b A(H5N8), a highly pathogenic avian influenza virus, from a worker during an outbreak on a poultry farm, Russia, December 2020.Euro Surveill. 2021; 262100439Crossref PubMed Scopus (34) Google Scholar highlighting the increasing threat to humans posed by the co-circulation of H5N6 and H5N8 viruses.Wild waterfowl are regarded as natural reservoirs that contribute to the global spread of avian influenza viruses through long-distance migration.1Wille M Barr IG Resurgence of avian influenza virus.Science. 2022; 376: 459-460Crossref PubMed Scopus (7) Google Scholar, 4Zhang J Li X Wang X et al.Genomic evolution, transmission dynamics, and pathogenicity of avian influenza A (H5N8) viruses emerging in China, 2020.Virus Evol. 2021; 7veab046Crossref Scopus (11) Google Scholar Frequent contact with wild birds remains the most probable cause of viral introduction into domestic poultry. Countries in the Middle East, Europe, and Asia have a particularly important role in the global dissemination of influenza viruses.4Zhang J Li X Wang X et al.Genomic evolution, transmission dynamics, and pathogenicity of avian influenza A (H5N8) viruses emerging in China, 2020.Virus Evol. 2021; 7veab046Crossref Scopus (11) Google Scholar The co-circulation of H5N6 and H5N8 viruses in migratory birds accelerated the evolution of novel variants. Nowadays, clade 2.3.4.4b H5 influenza viruses are widely prevalent in China. However, based on our assessment, the circulating 2.3.4.4b H5N6 viruses are antigenically distinct from the strains in the commercial vaccine in China (appendix pp 3–4, 29), suggesting that these novel viruses will continue to circulate in poultry if the commercial vaccine is not updated. The ongoing 2021–22 wave of avian influenza, which involves not only H5N6 but also the current outbreak of H5N1 viruses, is unprecedented in terms of its rapid spread and high frequency of outbreaks in birds, and poses a continuous threat to public health. First identified as belonging to the H5N1 subtype in Guangdong province, China, in 1996, the Gs/GD lineage H5 avian influenza viruses have continuously evolved and spread since.1Wille M Barr IG Resurgence of avian influenza virus.Science. 2022; 376: 459-460Crossref PubMed Scopus (7) Google Scholar, 2Dai M Yan N Huang Y Zhao L Liao M Survivability of highly pathogenic avian influenza virus on raw chicken meat in different environmental conditions.Lancet Microbe. 2022; 3: e92Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar H5 subtype viruses evolved into multiple distinct subclades, among which 2.3.4.4 has become dominant in China,3Yamaji R Saad MD Davis CT et al.Pandemic potential of highly pathogenic avian influenza clade 2.3.4.4 A(H5) viruses.Rev Med Virol. 2020; 30e2099Crossref PubMed Scopus (34) Google Scholar and H5N6 viruses of this subclade led to an apparent increase in human infections in 2021 and 2022. During this period, 33 cases (of a total of 76 recorded cases infected with subclade 2.3.4.4 H5N6 viruses) have been documented, resulting in 11 deaths and posing an alarming threat to public health.1Wille M Barr IG Resurgence of avian influenza virus.Science. 2022; 376: 459-460Crossref PubMed Scopus (7) Google Scholar Almost all confirmed cases were in individuals who had reported exposure to poultry. To address concerns regarding the sharp increase in the number of human infections, we explored the evolutionary dynamics and conducted a risk assessment of H5N6 viruses from birds in live poultry markets during 2021. In 2021, 5883 cloacal and tracheal swab samples from chickens, ducks, and geese were obtained from live poultry markets in China and analysed for influenza viruses (appendix pp 9–13). We determined the full-length genomes of 19 H5N6 viruses from chickens, ducks, and geese and found that the genomes of these viruses were more complex than those of H5N6 viruses circulating in China previously (appendix pp 2–3). Of particular concern is that the genomes of all H5N6 viruses were continuously reassorted with those of 2.3.4.4b H5N8 viruses of wild bird-origin, and were genetically closely related to the H5N6 virus that infected humans in 2021 (appendix pp 2–3, 14–28). We found that these 2.3.4.4b H5N6 viruses were novel reassortants. The HA and M genes of all isolates were derived from 2.3.4.4b H5N8 viruses of wild-bird origin, whereas other internal genes of all isolates exhibited several separate clusters. On the basis of phylogenetic trees, we identified five distinct genotypes of H5N6 viruses (G1–G5; appendix pp 3, 28), and found that both the G1 and G3 genotype H5N6 viruses were 100% lethal to mice (appendix pp 3–4, 28–29). The high genetic diversity and the virulence in mammals of H5N6 viruses in 2021 pose an increasing threat to public health. During the 2020–21 influenza season, novel H5N8 viruses repeatedly entered Europe, Russia, South Korea, and China, causing numerous outbreaks in wild birds and poultry.4Zhang J Li X Wang X et al.Genomic evolution, transmission dynamics, and pathogenicity of avian influenza A (H5N8) viruses emerging in China, 2020.Virus Evol. 2021; 7veab046Crossref Scopus (11) Google Scholar Notably, these H5N8 viruses infected humans in Russia,5Pyankova OG Susloparov IM Moiseeva AA et al.Isolation of clade 2.3.4.4b A(H5N8), a highly pathogenic avian influenza virus, from a worker during an outbreak on a poultry farm, Russia, December 2020.Euro Surveill. 2021; 262100439Crossref PubMed Scopus (34) Google Scholar highlighting the increasing threat to humans posed by the co-circulation of H5N6 and H5N8 viruses. Wild waterfowl are regarded as natural reservoirs that contribute to the global spread of avian influenza viruses through long-distance migration.1Wille M Barr IG Resurgence of avian influenza virus.Science. 2022; 376: 459-460Crossref PubMed Scopus (7) Google Scholar, 4Zhang J Li X Wang X et al.Genomic evolution, transmission dynamics, and pathogenicity of avian influenza A (H5N8) viruses emerging in China, 2020.Virus Evol. 2021; 7veab046Crossref Scopus (11) Google Scholar Frequent contact with wild birds remains the most probable cause of viral introduction into domestic poultry. Countries in the Middle East, Europe, and Asia have a particularly important role in the global dissemination of influenza viruses.4Zhang J Li X Wang X et al.Genomic evolution, transmission dynamics, and pathogenicity of avian influenza A (H5N8) viruses emerging in China, 2020.Virus Evol. 2021; 7veab046Crossref Scopus (11) Google Scholar The co-circulation of H5N6 and H5N8 viruses in migratory birds accelerated the evolution of novel variants. Nowadays, clade 2.3.4.4b H5 influenza viruses are widely prevalent in China. However, based on our assessment, the circulating 2.3.4.4b H5N6 viruses are antigenically distinct from the strains in the commercial vaccine in China (appendix pp 3–4, 29), suggesting that these novel viruses will continue to circulate in poultry if the commercial vaccine is not updated. The ongoing 2021–22 wave of avian influenza, which involves not only H5N6 but also the current outbreak of H5N1 viruses, is unprecedented in terms of its rapid spread and high frequency of outbreaks in birds, and poses a continuous threat to public health. We declare no competing interests. We acknowledge the authors and the originating and submitting laboratories of the sequences from GISAID's EpiFlu Database on which this research is based. All submitters of data can be contacted directly through the GISAID website (https://www.gisaid.org). This work was supported by the Guangdong Major Project of Basic and Applied Basic Research (2020B0301030007), the National Natural Science Foundation of China (31830097 and 31672586), the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2018, WQ), and the Young Scholars of Yangtze River Scholar Professor Program (2019, WQ). JZ, HY, ML, and WQ planned and conceptualised the laboratory work and wrote the Correspondence. HY and YL isolated the virus from samples and sequenced the genomes. JZ, HY, and YL conducted the animal experiments and antigenic analysis. JZ conducted bioinformatics analysis and data interpretation. ML and WQ provided the funding. JZ and HY contributed equally. Supplementary Material Download .pdf (1.79 MB) Help with pdf files Supplementary appendix Download .pdf (1.79 MB) Help with pdf files Supplementary appendix Survivability of highly pathogenic avian influenza virus on raw chicken meat in different environmental conditionsHighly pathogenic avian influenza (HPAI) viruses, such as H7N9 and H5N8, can cause huge economic losses in the poultry industry, and they can pose a serious risk to public health.1,2 In Japan, HPAI viruses have been repeatedly detected on raw poultry, reportedly transported by international flight passengers from China and Vietnam.1 Here, we report the survivability of HPAI viruses on raw chicken meat in different environmental conditions. Full-Text PDF Open Access